| First Author | Uche UU | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 12 | Pages | 3165-3179 |
| PubMed ID | 30429249 | Mgi Jnum | J:269891 |
| Mgi Id | MGI:6273026 | Doi | 10.1084/jem.20172018 |
| Citation | Uche UU, et al. (2018) PIK3IP1/TrIP restricts activation of T cells through inhibition of PI3K/Akt. J Exp Med 215(12):3165-3179 |
| abstractText | Phosphatidylinositol-3 kinases (PI3Ks) modulate cellular growth, proliferation, and survival; dysregulation of the PI3K pathway can lead to autoimmune disease and cancer. PIK3IP1 (or transmembrane inhibitor of PI3K [TrIP]) is a putative transmembrane regulator of PI3K. TrIP contains an extracellular kringle domain and an intracellular domain with homology to the inter-SH2 domain of the PI3K regulatory subunit p85, but the mechanism of TrIP function is poorly understood. We show that both the kringle and p85-like domains are necessary for TrIP inhibition of PI3K and that TrIP is down-modulated from the surface of T cells during T cell activation. In addition, we present evidence that the kringle domain may modulate TrIP function by mediating oligomerization. Using an inducible knockout mouse model, we show that TrIP-deficient T cells exhibit more robust activation and can mediate clearance of Listeria monocytogenes infection faster than WT mice. Thus, TrIP is a negative regulator of T cell activation and may represent a novel target for immune modulation. |
